Probing the Local Near-Field Intensity of Plasmonic Nanoparticles in the Mid-infrared Spectral Region.

The enhanced local field of gold nanoparticles (AuNPs) in mid-infrared spectral regions is essential for improving the detection sensitivity of vibrational spectroscopy and mediating photochemical reactions. However, it is still challenging to measure its intensity at subnanometer scales. Here, using the NO2 symmetric stretching mode (νNO2) of self-assembled 4-nitrothiophenol (4-NTP) monolayers on AuNPs as a model, we demonstrated that the percentage of excited νNO2 mode, determined by femtosecond time-resolved sum-frequency generation vibrational spectroscopy, allows us to directly detect the local field intensity of the AuNP surface in subnanometer ranges. The local-field intensity is tuned by AuNP diameters. An approximate 17-fold enhancement was observed for the local field on 80 nm AuNPs compared to the Au film. Additionally, the local field can regulate the anharmonicity of the νNO2 mode by synergistic effect with molecular orientation. This work offers a promising approach to probe the local field intensity distribution around plasmonic NP surfaces at subnanometer scales.

Association of metabolomics with PD-1 inhibitor plus chemotherapy outcomes in patients with advanced non-small-cell lung cancer.

BACKGROUND: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a standard treatment for patients with non-small cell lung cancer (NSCLC) lacking driver gene mutations. Reliable biomarkers are essential for predicting treatment outcomes. Emerging evidence from various cancers suggests that early assessment of serum metabolites could serve as valuable biomarkers for predicting outcomes. This study aims to identify metabolites linked to treatment outcomes in patients with advanced NSCLC undergoing first-line or second-line therapy with programmed cell death 1 (PD-1) inhibitors plus chemotherapy. METHOD: 200 patients with advanced NSCLC receiving either first-line or second-line PD-1 inhibitor plus chemotherapy, and 50 patients undergoing first-line chemotherapy were enrolled in this study. The 200 patients receiving combination therapy were divided into a Discovery set (n=50) and a Validation set (n=150). These sets were further categorized into respond and non-respond groups based on progression-free survival PFS criteria (PFS≥12 and PFS<12 months). Serum samples were collected from all patients before treatment initiation for untargeted metabolomics analysis, with the goal of identifying and validating biomarkers that can predict the efficacy of immunotherapy plus chemotherapy. Additionally, the validated metabolites were grouped into high and low categories based on their medians, and their relationship with PFS was analyzed using Cox regression models in patients receiving combination therapy. RESULTS: After the impact of chemotherapy was accounted for, two significant differential metabolites were identified in both the Discovery and Validation sets: N-(3-Indolylacetyl)-L-alanine and methomyl (VIP>1 and p<0.05). Notably, upregulation of both metabolites was observed in the group with a poorer prognosis. In the univariate analysis of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were associated with longer PFS (HR=0.59, 95% CI, 0.41 to 0.84, p=0.003), and a prolonged PFS was also indicated by lower levels of methomyl (HR=0.67, 95% CI, 0.47 to 0.96, p=0.029). In multivariate analyses of PFS, lower levels of N-(3-Indolylacetyl)-L-alanine were significantly associated with a longer PFS (HR=0.60, 95% CI, 0.37 to 0.98, p=0.041). CONCLUSION: Improved outcomes were associated with lower levels of N-(3-Indolylacetyl)-L-alanine in patients with stage IIIB-IV NSCLC lacking driver gene mutations, who underwent first-line or second-line therapy with PD-1 inhibitors combined with chemotherapy. Further exploration of the potential predictive value of pretreatment detection of N-(3-Indolylacetyl)-L-alanine in peripheral blood for the efficacy of combination therapy is warranted. STATEMENT: The combination of ICIs and chemotherapy has established itself as the new standard of care for first-line or second-line treatment in patients with advanced NSCLC lacking oncogenic driver alterations. Therefore, identifying biomarkers that can predict the efficacy and prognosis of immunotherapy plus chemotherapy is of paramount importance. Currently, the only validated predictive biomarker is programmed cell death ligand-1 (PD-L1), but its predictive value is not absolute. Our study suggests that the detection of N-(3-Indolylacetyl)-L-alanine in patient serum with untargeted metabolomics prior to combined therapy may predict the efficacy of treatment. Compared with detecting PD-L1 expression, the advantage of our biomarker is that it is more convenient, more dynamic, and seems to work synergistically with PD-L1 expression.

Probing the Molecular Structure and Dynamics of Membrane-Bound Proteins during Misfolding Processes by Sum-Frequency Generation Vibrational Spectroscopy.

Protein misfolding and amyloid formation are implicated in the protein dysfunction, but the underlying mechanism remains to be clarified due to the lack of effective tools for detecting the transient intermediates. Sum frequency generation vibrational spectroscopy (SFG-VS) has emerged as a powerful tool for identifying the structure and dynamics of proteins at the interfaces. In this review, we summarize recent SFG-VS studies on the structure and dynamics of membrane-bound proteins during misfolding processes. This paper first introduces the methods for determining the secondary structure of interfacial proteins: combining chiral and achiral spectra of amide A and amide I bands and combining amide I, amide II, and amide III spectral features. To demonstrate the ability of SFG-VS in investigating the interfacial protein misfolding and amyloid formation, studies on the interactions between different peptides/proteins (islet amyloid polypeptide, amyloid ß, prion protein, fused in sarcoma protein, hen egg-white lysozyme, fusing fusion peptide, class I hydrophobin SC3 and class II hydrophobin HFBI) and surfaces such as lipid membranes are discussed. These molecular-level studies revealed that SFG-VS can provide a unique understanding of the mechanism of interfacial protein misfolding and amyloid formation in real time, in situ and without any exogenous labeling.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Elimination of the fundamental mode hybridization on an x-cut lithium-niobate-on-insulator by using a densely packed bent waveguide array.

Lithium niobate (L i N b O 3, LN) is a promising material for integrated photonics due to its natural advantages. The commercialization of thin-film LN technology has revitalized this platform, enabling low-loss waveguides, micro-rings, and compact electro-optical modulators. However, the anisotropic birefringent nature of X-cut LN leads to mode hybridization of TE and TM modes, which is detrimental to most polarization-sensitive integrated optical waveguide devices. A novel structure, to the best of our knowldege, utilizing a densely packed bent waveguide array is presented in this paper to eliminate mode hybridization. The refractive index is modulated in a manner that eliminates the avoided crossing of the refractive index curves of the TE and TM fundamental modes; thus, mode hybridization is prevented. The structures are readily accessible in the full range of commercially available LN film thicknesses from 400 to 720 nm and in any etching depth. The proposed structures give a polarization extinction ratio of -30d B across all bend radii, while simultaneously maintaining low excess loss of less than -1d B after reaching a 100 µm bend radius.

Counterion-Mediated Hydrogen Bonding Making Poly(styrenesulfonate)-Based Strong Polyelectrolytes pH-Responsive.

Owing to the well-established fact that poly(styrenesulfonate) (PSS)-based strong polyelectrolytes are pH insensitive, their applications in smart materials have thus been severely limited. However, we demonstrate here that counterion-mediated hydrogen bonding (CMHB) makes the PSS brush pH-responsive. With decreasing pH, more hydrogen bonds are formed between the bound hydronium counterions and the sulfonate (-SO3-) groups in the PSS brush. At the microscale, the formation of more hydrogen bonds with decreasing pH leads to a more ordered structure and a larger tilt angle of the -SO3- groups in the PSS brush. On the other hand, a range of important physicochemical properties of the PSS brush, including hydration, stiffness, wettability, and adhesion, are responsive to pH, induced by the effect of CMHB on the PSS brush. Our work reveals a clear structure-property relationship for the pH-responsive PSS brush. This work not only provides a new understanding of the fundamental properties of the PSS brush but also greatly extends the applications of PSS-based strong polyelectrolytes.

On-treatment lung immune prognostic index is predictive for first-line PD-1 inhibitor combined with chemotherapy in patients with non-small cell lung cancer.

Background: Inflammation is a factor that promotes tumor progression and immunosuppression. Lung immune prognostic index (LIPI) is a non-invasive and easily calculated indicator of inflammation. This study aimed to investigate whether continuous assessment of LIPI has predictive value for chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients receiving first-line programmed cell death 1 (PD-1) inhibitor plus chemotherapy. In addition, the predictive value of LIPI in patients with the negative or low programmed death-ligand (PD-L1) expression level was also explored. Methods: Totally, 146 stage IIIB to IV or recurrent NSCLC patients who received first-line PD-1 inhibitor combined with chemotherapy were enrolled in this study. The LIPI scores were calculated at baseline (PRE-LIPI) and after two cycles of the combined administration (POST-LIPI). This study analyzed the relationship between good/intermediate/poor PRE (POST)-LIPI and objective response rate (ORR), as well as progression-free survival (PFS) using logistic and Cox regression models. In addition, the predictive value of LIPI in patients with the negative or low PD-L1 expression level was explored. To further assess the potential predictive value of continuous assessment of LIPI, the association of sum (LIPI) [sum(LIPI) = PRE-LIPI + POST-LIPI] and PFS was analyzed in the 146 patients. Results: Compared with good POST-LIPI group, significantly lower ORRs were found in intermediate POST-LIPI (P = 0.005) and poor POST-LIPI (P = 0.018) groups. Moreover, intermediate POST-LIPI (P =0.003) and poor POST-LIPI (P < 0.001) were significantly associated with a shorter PFS than good POST-LIPI. Additionally, a higher POST-LIPI score was still significantly associated with poorer treatment efficacy in patients with the negative or low PD-L1 expression level. Moreover, a higher sum (LIPI) score was significantly correlated with a shorter PFS (P = 0.001). Conclusion: Continuous assessment of LIPI might be an effective method for predicting the efficacy of PD-1 inhibitor plus chemotherapy in NSCLC patients. In addition, in patients with the negative or low PD-L1 expression level, it might also have a potential predictive value for therapeutic efficacy to continuously assess LIPI during the treatment.

The association of prokaryotic antiviral systems and symbiotic phage communities in drinking water microbiomes.

Prokaryotic antiviral systems are important mediators for prokaryote-phage interactions, which have significant implications for the survival of prokaryotic community. However, the prokaryotic antiviral systems under environmental stress are poorly understood, limiting the understanding of microbial adaptability. Here, we systematically investigated the profile of the prokaryotic antiviral systems at the community level and prokaryote-phage interactions in the drinking water microbiome. Chlorine disinfectant was revealed as the main ecological driver for the difference in prokaryotic antiviral systems and prokaryote-phage interactions. Specifically, the prokaryotic antiviral systems in the microbiome exhibited a higher abundance, broader antiviral spectrum, and lower metabolic burden under disinfectant stress. Moreover, significant positive correlations were observed between phage lysogenicity and enrichment of antiviral systems (e.g., Type IIG and IV restriction-modification (RM) systems, and Type II CRISPR-Cas system) in the presence of disinfection, indicating these antiviral systems might be more compatible with lysogenic phages and prophages. Accordingly, there was a stronger prokaryote-phage symbiosis in disinfected microbiome, and the symbiotic phages carried more auxiliary metabolic genes (AMGs) related to prokaryotic adaptability as well as antiviral systems, which might further enhance prokaryote survival in drinking water distribution systems. Overall, this study demonstrates that the prokaryotic antiviral systems had a close association with their symbiotic phages, which provides novel insights into prokaryote-phage interactions and microbial environmental adaptation.

A procedure in mice to obtain intact pituitary-infundibulum-hypothalamus preparations: a method to evaluate the reconstruction of hypothalamohypophyseal system.

PURPOSE: The histopathological study of brain tissue is a common method in neuroscience. However, efficient procedures to preserve the intact hypothalamic-pituitary brain specimens are not available in mice for histopathological study. METHOD: We describe a detailed procedure for obtaining mouse brain with pituitary-hypothalamus continuity. Unlike the traditional methods, we collect the brain via a ventral approach. We cut the intraoccipital synchondrosis, transection the endocranium of pituitary, broke the spheno-occipital synchondrosis, expose the posterior edge of pituitary, separate the trigeminal nerve, then the intact pituitary gland was preserved. RESULT: We report an more effective and practical method to obtain continuous hypothalamus -pituitary preparations based on the preserve of leptomeninges. COMPARED WITH THE EXISTING METHODS: Our procedure effectively protects the integrity of the fragile infundibulum preventing the pituitary from separating from the hypothalamus. This procedure is more convenient and efficient. CONCLUSION: We present a convenient and practical procedure to obtain intact hypothalamic-pituitary brain specimens for subsequent histopathological evaluation in mice.

Decreased monocyte-to-lymphocyte ratio was associated with satisfied outcomes of first-line PD-1 inhibitors plus chemotherapy in stage IIIB-IV non-small cell lung cancer.

Objectives: Immune-checkpoint inhibitors (ICIs) combined with chemotherapy are more widely used than monotherapy and have shown better survival in patients with advanced non-small cell lung cancer (NSCLC) without oncogenic driver alterations. The monocyte-to-lymphocyte ratio (MLR) might predict the treatment outcomes of ICI therapy in advanced NSCLC patients but has not yet been investigated. In addition, the cutoff of MLR is controversial. Therefore, the present study aimed to explore the associations between changes in MLR at the initial stage of treatment and clinical outcomes in stage IIIB-IV NSCLC patients receiving first-line PD-1 inhibitor combined with chemotherapy. Methods: The present study included 139 stage IIIB-IV NSCLC patients treated with first-line PD-1 inhibitor combined with chemotherapy. The blood results were assessed 10 days before initiation of PD-1 inhibitor-based combination therapy (time point 1, baseline) and before the third cycle of combined therapy (time point 2). Compared to altered MLR, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in baseline and in time point 2, patients were divided into decreased MLR/NLR/PLR and increased MLR/NLR/PLR groups. The objective response rate (ORR), progression-free survival (PFS), and the association with the changes in blood indicators were analyzed. Results: A total of 48 patients were categorized in the decreased MLR group and 91 in the increased MLR group. Patients with decreased MLR had a significantly higher ORR in the univariate (P<0.001) and multivariate (P<0.001) Cox proportional hazards models. On the other hand, decreased MLR was significantly associated with prolonged PFS in the univariate (P=0.007) and multivariate (P=0.016) analyses. Next, 91 patients comprised the decreased NLR group and 48 as the increased NLR group. Patients with decreased NLR exhibited high ORR (P=0.001) and prolonged PFS in univariate analysis (P=0.033). Then, 64 patients comprised the decreased PLR group and 75 the increased PLR group. Decreased PLR was significantly associated with high ORR in univariate (P<0.001) and multivariate (P=0.017) analyses. The subgroup analyses showed that decreased MLR was significantly associated with satisfactory outcomes in patients with all PD-L1 expressions. Conclusion: Decreased MLR was associated with high ORR and long PFS and might have a potential predictive value in patients with stage IIIB-IV NSCLC treated with first-line PD-1 inhibitor combined with chemotherapy. In addition, changes in MLR might have predictive value in all PD-L1-expressing populations. Decreased NLR and PLR also showed improved survival, suggesting that changes in NLR and PLR may be complementary to predicting prognosis.

Viral and Bacterial Communities Collaborate through Complementary Assembly Processes in Soil to Survive Organochlorine Contamination.

The ecological drivers that direct the assembly of viral and host bacterial communities are largely unknown, even though viral-encoded accessory genes help host bacteria survive in polluted environments. To understand the ecological mechanism(s) of viruses and hosts synergistically surviving under organochlorine pesticide (OCP) stress, we investigated the community assembly processes of viruses and bacteria at the taxon and functional gene levels in clean and OCP-contaminated soils in China using a combination of metagenomics/viromics and bioinformatics approaches. We observed a decreased richness of bacterial taxa and functional genes but an increased richness of viral taxa and auxiliary metabolic genes (AMGs) in OCP-contaminated soils (from 0 to 2,617.6 mg · kg-1). In OCP-contaminated soils, the assembly of bacterial taxa and genes was dominated by a deterministic process, of which the relative significance was 93.0% and 88.7%, respectively. In contrast, the assembly of viral taxa and AMGs was driven by a stochastic process, which contributed 83.1% and 69.2%, respectively. The virus-host prediction analysis, which indicated Siphoviridae was linked to 75.0% of bacterial phyla, and the higher migration rate of viral taxa and AMGs in OCP-contaminated soil suggested that viruses show promise for the dissemination of functional genes among bacterial communities. Taken together, the results of this study indicated that the stochastic assembly processes of viral taxa and AMGs facilitated bacterial resistance to OCP stress in soils. Moreover, our findings provide a novel avenue for understanding the synergistic interactions between viruses and bacteria from the perspective of microbial ecology, highlighting the significance of viruses in mediating bioremediation of contaminated soils. IMPORTANCE The interaction between viral communities and microbial hosts has been studied extensively, and the viral community affects host community metabolic function through AMGs. Microbial community assembly is the process by which species colonize and interact to establish and maintain communities. This is the first study that aimed to understand the assembly process of bacterial and viral communities under OCP stress. The findings of this study provide information about microbial community responses to OCP stress and reveal the collaborative interactions between viral and bacterial communities to resist pollutant stress. Thereby, we highlight the importance of viruses in soil bioremediation from the perspective of community assembly.

Virtual bronchoscopic navigation and endobronchial ultrasound with a guide sheath without fluoroscopy for diagnosing peripheral pulmonary lesions with a bronchus leading to or adjacent to the lesion: A randomized non-inferiority trial.

BACKGROUND AND OBJECTIVE: Transbronchial sampling of peripheral pulmonary lesions (PPLs) is routinely performed under fluoroscopy. However, advanced ancillary techniques have become available, such as virtual bronchoscopic navigation (VBN) and radial endobronchial ultrasound with a guide sheath (rEBUS-GS). This study was performed to determine whether the diagnostic utility of VBN and rEBUS with a GS is similar with or without fluoroscopy. METHODS: This multicenter non-inferiority trial randomized patients to a VBN-rEBUS-GS with or without fluoroscopy group at three centres. The primary endpoint was the diagnostic yield. The secondary endpoints were the time for rEBUS, GS, and the total operation. Complications were also recorded. RESULTS: Four hundred and ninety-six subjects were assessed and 426 subjects were included in the analysis (212 in non-fluoroscopy-guided-group and 214 in fluoroscopy-guided-group). The diagnostic yield in the non-fluoroscopy-guided-group (84.0%) was not inferior to that in the fluoroscopy-guided-group (84.6%), with a diagnostic difference of -0.6% (95% CI: -6.4%, 5.2%). Multivariable analysis confirmed that bronchus sign and lesion nature were valuable diagnostic predictors in non-fluoroscopy-guided-group. The non-fluoroscopy-guided-group had shorter rEBUS, GS, and total operation time. No severe complications occurred in either group. CONCLUSION: Transbronchial diagnosis of PPLs suspicious of malignancy and presence of a bronchus leading to or adjacent to lesions using VBN-rEBUS-GS without fluoroscopy is a safe and effective method that is non-inferior to VBN-rEBUS-GS with fluoroscopy. Bronchus leading to lesions and malignant nature are associated with high diagnostic yield in VBN-rEBUS-GS without fluoroscopy for the diagnosis of PPLs.

Development and validation of the artificial intelligence (AI)-based diagnostic model for bronchial lumen identification.

Background: Bronchoscopy is a key step in the diagnosis and treatment of respiratory diseases. However, the level of expertise varies among different bronchoscopists. Artificial intelligence (AI) may help them identify bronchial lumens. Thus, a bronchoscopy quality-control system based on AI was built to improve the performance of bronchoscopists. Methods: This single-center observational study consecutively collected bronchoscopy videos from Shanghai Chest Hospital and segmented each video into 31 different anatomical locations to develop an AI-assisted system based on a convolutional neural network (CNN) model. We then designed a single-center trial to compare the accuracy of lumen recognition by bronchoscopists with and without the assistance of the AI system. Results: A total of 28,441 qualified images of bronchial lumen were used to train the CNNs. In the cross-validation set, the optimal accuracy of the six models was between 91.83% and 96.62%. In the test set, the visual geometry group 16 (VGG-16) achieved optimal performance with an accuracy of 91.88%, and an area under the curve of 0.995. In the clinical evaluation, the accuracy rate of the AI system alone was 54.30% (202/372). For the identification of bronchi except for segmental bronchi, the accuracy was 82.69% (129/156). In group 1, the recognition accuracy rates of doctors A, B, a and b alone were 42.47%, 34.68%, 28.76%, and 29.57%, respectively, but increased to 57.53%, 54.57%, 54.57%, and 46.24% respectively when combined with the AI system. Similarly, in group 2, the recognition accuracy rates of doctors C, D, c, and d were 37.90%, 41.40%, 30.91%, and 33.60% respectively, but increased to 51.61%, 47.85%, 53.49%, and 54.30% respectively, when combined with the AI system. Except for doctor D, the accuracy of doctors in recognizing lumen was significantly higher with AI assistance than without AI assistance, regardless of their experience (P<0.001). Conclusions: Our AI system could better recognize bronchial lumen and reduce differences in the operation levels of different bronchoscopists. It could be used to improve the quality of everyday bronchoscopies.

Experimental Insight into the Enigmatic Persistence of Marine Refractory Dissolved Organic Matter.

More than 90% of marine dissolved organic matter (DOM) is biologically recalcitrant. This recalcitrance has been attributed to intrinsically refractory molecules or to low concentrations of molecules, but their relative contributions are a long-standing debate. Characterizing the molecular composition of marine DOM and its bioavailability is critical for understanding this uncertainty. Here, using different sorbents, DOM was solid-phase extracted from coastal, epipelagic, and deep-sea water samples for molecular characterization and was subjected to a 180-day incubation. 1H nuclear magnetic resonance spectroscopy and ultra-high-resolution mass spectrometry (UHRMS) analyses revealed that all of the DOM extracts contained refractory carboxyl-rich alicyclic molecules, accompanied with minor bio-labile components, for example, carbohydrates. Furthermore, dissolved organic carbon concentration analysis showed that a considerable fraction of the extracted DOM (86-95%) amended in the three seawater samples resisted microbial decomposition throughout the 180-day heterotrophic incubation, even when concentrated threefold. UHRMS analysis revealed that DOM composition remained mostly invariant in the 180-day deep-sea incubations. These results underlined that the dilution and intrinsic recalcitrance hypotheses are not mutually exclusive in explaining the recalcitrance of oceanic DOM, and that the intrinsically refractory DOM likely has a relatively high contribution to the solid-phase extractable DOM in the ocean.

Electrical Impedance Analysis for Lung Cancer: A Prospective, Multicenter, Blind Validation Study.

Hypothesis: Patients with cancer have different impedances or conductances than patients with benign normal tissue; thus, we can apply electrical impedance analysis (EIA) to identify patients with cancer. Method: To evaluate EIA's efficacy and safety profile in diagnosing pulmonary lesions, we conducted a prospective, multicenter study among patients with pulmonary lesions recruited from 4 clinical centers (Zhongshan Hospital Ethics Committee, Approval No. 2015-16R and 2017-035(3). They underwent EIA to obtain an Algorithm Composite Score or 'Prolung Index,' PI. The classification threshold of 29 was first tested in an analytical validation set of 144 patients and independently validated in a clinical validation set of 418 patients. The subject's final diagnosis depended on histology and a 2-year follow-up. Results: In total, 418 patients completed the entire protocol for clinical validation, with 186 true positives, 145 true negatives, 52 false positives, and 35 false negatives. The sensitivity, specificity, and diagnostic yield were 84% (95% CI 79.3%-89.0%), 74% (95% CI 67.4%-79.8%), and 79% (95%CI 75.3%-83.1%), respectively, and did not differ according to age, sex, smoking history, body mass index, or lesion types. The sensitivity of small lesions was comparable to that of large lesions (p = 0.13). Four hundred eighty-four patients who underwent the analysis received a safety evaluation. No adverse events were considered to be related to the test. Conclusion: Electrical impedance analysis is a safe and efficient tool for risk stratification of pulmonary lesions, especially for patients with a suspicious lung lesion.

A Novel Electromagnetic Navigation Bronchoscopy System for the Diagnosis of Peripheral Pulmonary Nodules: A Randomized Clinical Trial.

Rationale: Endobronchial ultrasound (EBUS) combined with a guide sheath (GS) as an instrument for confirming the proximity of the bronchoscope and its relationship to the lesion can increase the diagnostic yield when conducting transbronchial lung biopsy of peripheral pulmonary nodules (PPNs). A novel electromagnetic navigational bronchoscopy (ENB) system comprising a thinner locatable sensor probe as a guidance instrument was developed to be suitable for a thin bronchoscope with a working channel 2 mm in diameter. The diagnostic efficacy of EBUS-GS with or without this ENB system has not been confirmed. Objectives: To compare the diagnostic value and safety of EBUS-GS with or without the ENB system for diagnosing PPNs. Methods: A prospective, multicenter, randomized controlled clinical trial was designed and conducted at three centers. Patients with PPNs suspected to be malignant were enrolled and randomly assigned to the ENB-EBUS-GS group or the EBUS-GS group. The primary endpoint was the diagnostic yield in each group. The secondary endpoint was the procedural time and other factors affecting diagnostic yield. The safety endpoint was procedural complications. Results: Four hundred participants were enrolled from July 2018 to October 2019, and 385 patients were analyzed, 193 in the ENB-EBUS-GS group and 192 in the EBUS-GS group. The mean nodule size was 21.7 ± 5.3 mm. The diagnostic yields were 82.9% (95% confidence interval [CI], 77.6-88.2%) in the ENB-EBUS-GS group and 73.4% (95% CI, 67.2-79.7%) in the EBUS-GS group. The difference between the two groups was 9.5% (95% CI, 2.6-16.3%), with an adjusted difference of 9.0% (95% CI, 2.3-15.8%) after adjusting for the stratification factors and center. The time to find lesions in the ENB-EBUS-GS group was shorter than in the EBUS-GS group (213.2 ± 145.6 vs. 264.8 ± 189.5 s; P = 0.003). Intraoperative hemorrhage occurred 3.6% of subjects in the ENB-EBUS-GS group and 3.1% in the EBUS-GS group, without significant differences between the two groups. Conclusions: The novel ENB system combined with EBUS-GS demonstrated improved ability to locate PPNs, achieving a high diagnostic yield for PPNs compared with EBUS-GS alone in a safe and efficient procedure. Clinical trial registered with www.clinicaltrials.gov (NCT03569306).

Classification of unilateral thalamic gliomas predicts tumor resection and patient's survival: a single center retrospective study.

BACKGROUND: To propose our classification about unilateral thalamic gliomas, and to describe relationship between the classification and clinical characteristics including symptoms, surgical approaches and survival, which should contribute to the treatment and the prognostic prediction of unilateral thalamic gliomas. METHODS: A total of 66 adult unilateral thalamic glioma patients with pathologic confirmation between January 2010 and December 2018 were retrospectively investigated. RESULTS: Unilateral thalamic gliomas could be divided into quadrigeminal cistern and ventricle extension type (Type Q), lateral type (Type L) and anterior type (Type A) according to tumor location, extensive polarity and location of ipsilateral posterior limb of internal capsule. Each subtype of QLA classification could match with one kind of corresponding approach. Preoperative symptoms including headache, dyskinesia, aphasia, hydrocephalus and KPS scores, and pathological features including H3K27M mutation and P53 expression were correlated with QLA classification. Further analysis confirmed that Type Q tumors had a higher rate of total resection and a significantly longer survival time compared to Type L and Type A tumors, with similar improved and deteriorated rates of symptoms. Univariate and multivariate analysis demonstrated QLA classification was remarkedly associated with overall survival and could be considered as an independent prognostic factor in patients with unilateral thalamic gliomas. CONCLUSIONS: Unilateral thalamic glioma could be divided into 3 subtypes by imaging characteristics, symptoms and survival. QLA classification could predict tumor resection and the prognosis and could contribute to the planning of therapeutic strategy in patients with unilateral thalamic gliomas.

A Classifier for Improving Early Lung Cancer Diagnosis Incorporating Artificial Intelligence and Liquid Biopsy.

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans' Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery. Clinical Trial Registration Number: ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.

Contrasted effects of Metaphire guillelmi on tetracycline diffusion and dissipation in soil.

Earthworms are important in soil bioremediation because of their capability of pollutant degradation. However, the trade-off between pollutant dissemination and degradation arising from earthworm activities remains unclear, as well as the potential biodegradation mechanism. Herein, an earthworm avoidance experiment was established to investigate Metaphire guillelmi-mediated tetracycline (TC) diffusion and degradation. The results showed that above 1600 mg kg-1 TC pollution in soil induced avoidance behaviour of earthworms (p < 0.05), below which the random worm behaviour accelerated TC diffusion by 8.2% at most (p < 0.05), resulting in elevated levels of antibiotic-resistant bacteria and genes in the soil. Nevertheless, earthworms enhanced TC degradation regardless of whether their avoidance behaviour occurred (14.6-25.8%, p < 0.05). Compared with in soil, metabolic pathways affiliated with xenobiotic degradation and metabolism in the intestines were enriched (LDA >3). Given the abundant glutathione S-transferases in the intestines and their close relationship with Δ degradation, they may play a key role in intestinal TC biodegradation. In general, earthworms had good tolerance to soil TC contamination and their impact on promoting TC degradation outweighed that accelerating TC diffusion. This work provides a comprehensive view of earthworms as a potential remediation method for TC-contaminated soil.